Abstract

Human lipocortin-I (hLC1), when was expressed as a secretory product in Saccharomyces cerevisiae, was cleaved to a significant extent by endoproteolytic processing, resulting in the accumulation of des1-26-hLC1 in the culture supernatant. This proteolytic cleavage was inhibited significantly by the addition of high concentrations of L-arginine and L-lysine, with a resultant marked improvement in the yield of intact hLC1. When the hLC1 was expressed in S. cerevisiae mutants deficient in one or two of the following endoproteases, Kex2p, Mkc7p and Yps1p (Yap3p), the mutants exhibited no reduction in the extent of hLC1 proteolysis, indicating that these endoproteases are not involved in the proteolytic cleavage of hLC1.